RESUMO
The Vilsmeier formylation has been introduced for the solid-phase functionalization of five different 2-carboxyindoles. The aldehyde functionality has been utilized in the preparation of O-benzylhydroxyureas.
Assuntos
Técnicas de Química Combinatória , Hidroxiureia/síntese química , Indóis/síntese química , Ureia/análogos & derivados , Ureia/síntese química , Ácidos Carboxílicos/síntese química , Desenho de Fármacos , Formiatos/química , Tecnologia FarmacêuticaRESUMO
As part of an ongoing lead discovery project we have developed a convenient method for the modification and substitution of indole moieties at the 3-position. Selective bromination of three different 2-carboxyindoles was followed by Suzuki cross-coupling with aryl and heteroaryl boronic acids on a Merrifield resin solid-phase. After column chromatography, yields of the 3- substituted indoles ranged from 42-98%.
Assuntos
Bromo , Indóis/química , Indóis/síntese química , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-AtividadeRESUMO
Tandem mass spectrometric behaviour was studied for a small combinatorial library of alkyl 3-hydroxy-5-(4'-nitrophenoxy) benzoates (A1-A5) and alkyl 3-hydroxy-5-(2', 4'-dinitrophenoxy) benzoates (B1-B5). The spectra were recorded by negative ion electrospray low-energy collision induced dissociation (CID) tandem mass spectrometry. The product ion spectra of [M - H](-) of the benzoates A1-A5 are similar, as are those of benzoates B1-B5. However, the spectra of the B series compounds differ significantly from those of the A series owing to the second electron-withdrawing nitro substituent in the B compounds. In addition, the length of the alkyl chain has an effect on the fragmentation. However, both series of compounds exhibit an abundant nitrophenoxy ion formed by the loss of 3-hydroxybenzoate. This is at m/z 138 in A1-A5 and at m/z 183 in B1-B5. A precursor ion scan of the nitrophenoxy ion provides a rapid method to identify the synthesised compounds in this type of combinatorial mixture. Copyright 1999 John Wiley & Sons, Ltd.